Prevalence and Patient Characteristics of Ectodermal Dysplasias in Denmark.

Importance: Ectodermal dysplasias constitute a group of rare genetic disorders of the skin and skin appendages with hypodontia, hypotrichosis, and hypohidrosis as cardinal features. There is a lack of population-based research into the epidemiology of ectodermal dysplasias. Objective: To establish a validated population-based cohort of patients with ectodermal dysplasia in Denmark and to assess the disease prevalence and patient characteristics. Design, Setting, and Participants: This nationwide cohort study used individual-level registry data recorded across the Danish universal health care system to identify patients with ectodermal dysplasias from January 1, 1995, to August 25, 2021. A 3-level search of the Danish National Patient Registry and the Danish National Child Odontology Registry was conducted to identify patients with diagnosis codes indicative of ectodermal dysplasias; patients registered in the Danish RAREDIS Database, the Danish Database of Genodermatoses, and local databases were also added. The search results underwent diagnosis validation and review of clinical data using medical records. Of 844 patient records suggestive of ectodermal dysplasias, 791 patients (93.7%) had medical records available for review. Positive predictive values of the diagnosis coding were computed, birth prevalence was estimated, and patient characteristics were identified. Data analysis was performed from May 4 to December 22, 2023. Results: The identified and validated study cohort included 396 patients (median [IQR] age at diagnosis, 13 [4-30] years, 246 females [62.1%]), of whom 319 had confirmed ectodermal dysplasias and 77 were likely cases. The combined positive predictive value (PPV) for ectodermal dysplasia-specific diagnosis codes was 67.0% (95% CI, 62.7%-71.0%). From 1995 to 2011, the estimated minimum birth prevalence per 100 000 live births was 14.5 (95% CI, 12.2-16.7) for all ectodermal dysplasias and 2.8 (95% CI, 1.8-3.8) for X-linked hypohidrotic ectodermal dysplasias. A molecular genetic diagnosis was available for 241 patients (61%), including EDA (n = 100), IKBKG (n = 55), WNT10A (n = 21), TRPS1 (n = 18), EDAR (n = 10), P63 (n = 9), GJB6 (n = 9), PORCN (n = 7), and other rare genetic variants. Conclusions and Relevance: The findings of this nationwide cohort study indicate that the prevalence of ectodermal dysplasias was lower than previously reported. Furthermore, PPVs of the search algorithms emphasized the importance of diagnosis validation. The establishment of a large nationwide cohort of patients with ectodermal dysplasias, including detailed clinical and molecular data, is a unique resource for future research in ectodermal dysplasias.

Skin Cancer Development Is Strongly Associated with Actinic Keratosis in Solid Organ Transplant Recipients: A Danish Cohort Study.

BACKGROUND AND OBJECTIVES: Solid organ transplant recipients (SOTRs) are at increased risk of skin cancer and suffer from greater disease-specific morbidity and mortality. To risk stratify the expanding SOTR population for more targeted skin cancer screening, a detailed understanding of risk factors is needed. Using combined clinical and pathological data to capture prevalence of actinic keratosis (AK) and skin cancer, this study aimed to identify risk factors of skin cancer development in a Danish SOTR cohort. METHODS: The trial comprised a retrospective cohort study of patients attending organ transplant clinics at the dermatological departments of Bispebjerg and Gentofte Hospitals in Copenhagen, Denmark, between 2009 and 2021. In addition to pathology records, AK prevalence was determined by review of electronic medical records (EMRs) of SOTR visits which specifically included descriptions of clinical AK. Prevalence of skin cancer, here defined as basal cell carcinoma (BCC), squamous cell carcinoma (SCC) (invasive or in situ), or melanoma (invasive or in situ), was determined by EMR and pathology code review. Additional data extracted from EMRs included age, sex, Fitzpatrick skin type, transplantation date and type, and immunosuppressive therapy. The effect of risk factors on skin cancer was calculated by Cox proportional hazards regression. RESULTS: A total of 822 SOTRs were included with a mean follow-up duration of 10.8 years (SD 2.4 years). A skin dysplasia diagnosis was identified in 30% (n = 250) of the population, consisting of either AK (22%; n = 177), skin cancer (23%; n = 186) or both (14%; n = 113). An AK diagnosis predicted both SCC (odds ratio [OR]: 31.5 [95% CI: 9.8-100.6], p < 0.0001) and BCC development (OR: 2.3 [95% CI: 1.6-3.3], p < 0.0001), with AKs diagnosed an average 3.1 years before the first SCC (p < 0.0001). Correspondingly, while the risk of SCC in SOTRs without AK was 1.4% 25 years after transplantation, SOTRs with AKs had a 23% SCC risk only 10 years posttransplant. Other identified risk factors included Fitzpatrick skin type I (BCC: OR: 2.4 [95% CI: 1.2-5.0], p = 0.018; SCC: 3.2 [95% CI: 1.2-8.2], p = 0.016) and transplantation duration >15 years (BCC: OR: 1.8 [95% CI: 1.2-2.7], p = 0.007). No significant association between skin cancer development and sex or immunosuppressive regimen was shown. CONCLUSION: Keratinocyte carcinoma is strongly associated with an AK diagnosis in SOTRS and should prompt intensified skin cancer screening in affected individuals.

Genotype-phenotype associations in Danish patients with ocular and oculocutaneous albinism.

BACKGROUND: The study aimed to describe genotype-phenotype associations in patients with oculocutaneous and ocular-only albinism and to evaluate a set of diagnostic criteria proposed recently by Kruijt et al. MATERIALS AND METHODS: Genotype-phenotype associations in patients with a clinical diagnosis of albinism were studied based on imaging of hair and ocular features (nystagmus, iris color and translucency, fundus pigmentation and foveal development) and self-evaluated skin type. Patients were sub-grouped based on genetic findings. RESULTS: Patients with biallelic variants in TYR (n = 29), OCA2 (n = 22), other albinism genes (n = 13) or monoallelic variants in GPR143 (n = 13) were included as were 15 patients with a pure clinical diagnosis but no genetic findings. In descending order the most common findings were: foveal hypoplasia (any hypoplasia 95.2%, severe 88.0%), nystagmus (93.5%), iris translucency (any translucency 80.2%, moderate to severe 31.5%), misrouting on VEP (80.0%): fundus hypopigmentation (any hypopigmentation: 75.8%, severe 30.1%), fair skin type (73.8%), blue irides (62.0%), blonde hair (57.5%), and unpigmented eye lashes (39.1%). There were no phenotypic differences between the different genetic subgroups of albinism but patients with a pathogenic haplotype in TYR in combination with a classic variant had less iris translucency than patients with two classic variants in TYR. CONCLUSIONS: Ocular developmental features were the most common findings whereas phenotypic features related to pigmentation were less common findings but there were no genotype-phenotype correlations. All patients with a genetically confirmed diagnosis of albinism fulfilled the diagnostic criteria by Kruijt irrespective of genetic subtype.

Novel SUFU Frameshift Variant Leading to Meningioma in Three Generations in a Family with Gorlin Syndrome.

Gorlin syndrome is mainly caused by pathogenic germline variants in the tumour suppressor genes PTCH1 and SUFU, both regulatory genes in the hedgehog pathway. However, the phenotypes of patients with PTCH1 and SUFU pathogenic variants seem to differ. We present a family with a frameshift variant in the SUFU gene c.954del, p.Asn319Thrfs∗42 leading to meningiomas and multiple basal cell-carcinomas.

The Danish Nonmelanoma Skin Cancer Dermatology Database.

AIM OF DATABASE: The Danish Nonmelanoma Skin Cancer Dermatology Database was established in 2008. The aim of this database was to collect data on nonmelanoma skin cancer (NMSC) treatment and improve its treatment in Denmark. NMSC is the most common malignancy in the western countries and represents a significant challenge in terms of public health management and health care costs. However, high-quality epidemiological and treatment data on NMSC are sparse. STUDY POPULATION: The NMSC database includes patients with the following skin tumors: basal cell carcinoma (BCC), squamous cell carcinoma, Bowen's disease, and keratoacanthoma diagnosed by the participating office-based dermatologists in Denmark. MAIN VARIABLES: Clinical and histological diagnoses, BCC subtype, localization, size, skin cancer history, skin phototype, and evidence of metastases and treatment modality are the main variables in the NMSC database. Information on recurrence, cosmetic results, and complications are registered at two follow-up visits at 3 months (between 0 and 6 months) and 12 months (between 6 and 15 months) after treatment. DESCRIPTIVE DATA: In 2014, 11,522 patients with 17,575 tumors were registered in the database. Of tumors with a histological diagnosis, 13,571 were BCCs, 840 squamous cell carcinomas, 504 Bowen's disease, and 173 keratoakanthomas. CONCLUSION: The NMSC database encompasses detailed information on the type of tumor, a variety of prognostic factors, treatment modalities, and outcomes after treatment. The database has revealed that overall, the quality of care of NMSC in Danish dermatological clinics is high, and the database provides the necessary data for continuous quality assurance.

[Malignant adnexal carcinomas of the skin].

Malignant adnexal carcinomas of the skin are rare but associated with high propensity for local recurrence, and for some of the distinct subgroups they are known to metastasize regionally or distant. Biopsy is necessary for correct diagnosis, as the lesions cannot be separated from other tumour types entirely on their clinical appearance. The histologic diagnosis is troublesome, and the lesions are often mistaken for their benign counterpart, basal cell carcinoma or squamous cell carcinoma. The lesions are treated with surgery. Radiotherapy and chemotherapy may play a role in treatment, although the evidence is limited.

[Bullous pemphigoid may also be seen in children]. / Bulløs pemfigoid rammer også yngre patienter.

Bullous pemphigoid is most commonly seen in elderly patients, however, an increasing number of cases in children have been reported. In this article we present a case of a five-month-old boy who was admitted with red annular plaques over his entire body and vesicles and bullae on his hands and feet. Correct diagnosis was made by skin biopsy and after reviewing the literature high dose oral steroids therapy (1 mg/kg/day) was successfully initiated. The cause of the disease remains unknown. With correct treatment the prognosis is good with documented ten-year follow-up without relapse.

A massive neglected giant basal cell carcinoma in a schizophrenic patient treated successfully with vismodegib.

The small molecule vismodegib is a great treatment alternative to patients challenged, e.g. psychiatric disorders, suffering from severe basal cell carcinoma of the skin in which surgery or other treatment modalities is not possible because of patient's wish or condition. We present a case of a 73-year-old schizophrenic patient with a 15-year history of a neglected tumour located at the forehead and scalp, admitted to hospital in a state of inanition because of tumour expansion to the meninges and severe anaemia caused by bleeding, treated successfully with vismodegib.

Itch severity and quality of life in patients with pruritus: preliminary validity of a Danish adaptation of the itch severity scale.

The aim of this study was to examine the validity of a Danish adaptation of the Itch Severity Scale (ISS) by exploring the associations between pruritus severity, psychological symptoms, and quality of life in a consecutively recruited sample of 20 patients with atopic dermatitis, 20 with psoriasis, 20 with urticaria, 12 with genital pruritus, 11 with nephrogenic pruritus, and 20 controls with vascular malformations. Convergent and discriminative validity was explored by analysing the associations of the ISS total score and the individual ISS component scores with age, sex, diagnosis, disease severity, sleep quality, depressive symptoms, anxiety, non-specific somatic symptoms, and pruritus-related quality of life impairment. Patients with urticaria reported significantly (p < 0.05) greater pruritus severity scores than the remaining patient groups, and pruritus severity was significantly associated with impaired sleep quality, more depressive symptoms, higher levels of anxiety, more non-specific somatic symptoms, and impaired quality of life. The results also confirmed the multidimensional nature of pruritus, with the affective dimension of pruritus being a better predictor of depressive symptoms, anxiety, and quality of life impairment than the sensory dimension. Finally, our results confirmed previous findings that the associations between pruritus severity and depressive symptoms and somatic symptoms were partly mediated by the effect of pruritus on sleep quality.

Affective and sensory dimensions of pruritus severity: associations with psychological symptoms and quality of life in psoriasis patients.

The subjective dimensions of pruritus and their associations with psychological symptoms and quality of life were explored in a sample of 40 psoriasis patients. The patients completed a scale with descriptors from the Structured Itch Questionnaire together with measures of depression, distress, sleep quality and pruritus-related quality of life. Psoriasis severity was assessed with the Psoriasis Area and Severity Index. Factor analysis of descriptors confirmed both an affective and a sensory pruritus severity dimension. Multivariate statistics, controlling for age, gender, disease duration and severity, showed affective, but not sensory, pruritus severity to be a significant predictor of depressive symptoms, global distress, impairment of sleep, and pruritus-related quality of life. Mediation analyses indicated that impaired sleep quality partly mediated the association between pruritus severity and psychological symptoms. The results confirm that pruritus is multidimensional and indicate that the affective dimension may be the most important predictor of pruritus-related psychological morbidity, and that the association may be mediated by its negative impact on sleep quality.

Reproductive factors and extreme levels of maternal serum alpha-fetoprotein: a population-based study.

BACKGROUND: Levels of maternal alpha-fetoprotein (AFP) are increased during multiple gestations and preeclampsia but little is known regarding AFP levels in relation to other reproductive factors. Consequently, the objective of this work was to describe the possible relationship between AFP levels during pregnancy and maternal age at birth, maternal age at first birth, parity, time since previous birth and gender of the offspring. METHODS: Based on national registries we obtained the reproductive history on a population-based cohort of 44 227 women who had serum AFP levels determined in gestational weeks 14-21 and whose present and previous pregnancies resulted in live-born singletons. RESULTS: Many previous births and an interval of less than 2 years since last birth were significantly associated with extremely low levels of AFP in the mother. However, age at first birth and age at present pregnancy did not influence the AFP level. Women who gave birth to a girl had AFP levels that were 5%[95% confidence interval (CI) 4-6%] lower than those of women who had a boy. Adjustment for birthweight did not significantly affect the estimate. CONCLUSIONS: Low serum AFP levels in pregnancy are significantly correlated with high parity and with a short interval between births. The significantly lower levels of AFP in women who gave birth to girls could indicate a possible gender-specific regulatory mechanism.